To study the chemical constituents in ethanol extract of Cornus officinalis and their neuroprotective activity. The chemical constituents exerted neuroprotective effect were isolated and purified by normal phase silica gel column chromatography, Sephadex LH-20 gel column chromatography, macroporous resin, normal and reverse phase, cyanide silica gel LPLC (low pressure liquid chromatograph), and reverse phase HPLC, etc. Their structures were identified based on nuclear magnetic resonance spectrum, mass spectrum and published data, and their neuroprotective acitivity were evaluated by H₂O₂ induced SH-SY5Y damage cell model. The results showed that nine compounds were isolated from Cornus officinalis and identified as 7-β-morroniside (1), 7-β-O-methylmorroniside (2), 7-α-O-methylmorroniside (3), kingiside (4), cornolactones D (5), pollenfuran A (6), threo-2,3-bis (4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol (7), 5-hydroxymethyl furfural (8) and 3,4-dihydroxybenzoic acid (9). Among them, pollenfuran A (6) and threo-2,3-bis (4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol (7) were isolated from Cornus for the first time, and cornolactones D (5) was identified from Cornus officinalis for the first time. Compounds 7-β-morroniside (1), 7-β-O-methylmorroniside (2), and 7-α-O-methylmorroniside (3) exhibited neuroprotective effect.